Subbiah S, Harrison S C
Howard Hughes Medical Institute, Harvard University, Cambridge, MA 02138.
J Mol Biol. 1989 Oct 20;209(4):539-48. doi: 10.1016/0022-2836(89)90592-5.
A method that performs multiple sequence alignment by cyclical use of the standard pairwise Needleman-Wunsch algorithm is presented. The required central processor unit time is of the same order of magnitude as the standard Needleman-Wunsch pairwise implementation. Comparison with the one known case where the optimal multiple sequence alignment has been rigorously determined shows that in practice the proposed method finds the mathematically optimal solution. The more interesting question of the biological usefulness of such multiple sequence alignment over pairwise approaches is assessed using protein families whose X-ray structures are known. The two such cases studied, the subdomains of the ricin B-chain and the S-domains of virus coat proteins, have low pairwise similarity and thus fail to align correctly under standard pairwise sequence comparison. In both cases the multiple sequence alignment produced by the proposed technique, apart from minor deviations at loop regions, correctly predicts the true structural alignment. Thus, given many sequences of low pairwise similarity, the proposed multiple sequence method, can extract any familial similarity and so produce a sequence alignment consistent with the underlying structural homology.
提出了一种通过循环使用标准的成对Needleman-Wunsch算法来进行多序列比对的方法。所需的中央处理器单元时间与标准的Needleman-Wunsch成对实现处于同一数量级。与已严格确定最优多序列比对的一个已知案例进行比较表明，在实际应用中，所提出的方法找到了数学上的最优解。使用已知X射线结构的蛋白质家族来评估这种多序列比对相对于成对方法在生物学上的有用性这一更有趣的问题。所研究的两个这样的案例，蓖麻毒蛋白B链的亚结构域和病毒衣壳蛋白的S结构域，成对相似性较低，因此在标准的成对序列比较下无法正确比对。在这两种情况下，所提出的技术产生的多序列比对，除了在环区有微小偏差外，正确地预测了真实的结构比对。因此，对于许多成对相似性较低的序列，所提出的多序列方法可以提取任何家族相似性，从而产生与潜在结构同源性一致的序列比对。
